Scientists have developed a novel technique to trace the life history of individual cells back to their origins in a fertilized egg. By looking at the copy of the human genome present in healthy cells, they say they were able to build a picture of each cell's development from the early embryo on its journey to become part of an adult organ.
More specifically, by looking at the numbers and types of mutations in a cell's DNA, the researchers were able to assess whether the cell had divided a few times or many times and detect genetic signatures of the processes of DNA damage and repair that the cells had been exposed to during the life of the individual. Furthermore, comparing each cell's mutations with those of other cells in the body enabled scientists to map out a detailed tree of development from the fertilized egg.
"With this novel approach, we can peer back into an organism's development," noted Sam Behjati, Ph.D., from the Wellcome Trust Sanger Institute. "If we can better understand how normal, healthy cells mutate as they divide over a person's lifetime, we will gain a fundamental insight into what can be considered normal and how this differs from what we see in cancer cells."
His team’s paper ("Genome sequencing of normal cells reveals developmental lineages and mutational processes") appears in Nature.
The scientists looked at mouse cells from the stomach, small bowel, large bowel, and prostate. The single cells were grown to produce enough DNA to be sequenced. Eventually, single-cell sequencing technology will develop so that this type of experiment can be conducted using just one cell, according to Dr. Behjati. However, the tiny amounts of DNA in single cells mean that mutation data are not currently precise enough to reconstruct accurate lineages.
"Using somatic base substitutions, we reconstructed the early cell divisions of each animal, demonstrating the contributions of embryonic cells to adult tissues," wrote the investigators. "Differences were observed between tissues in the numbers and types of mutations accumulated by each cell, which likely reflect differences in the number of cell divisions they have undergone and varying contributions of different mutational processes. If somatic mutation rates are similar to those in mice, the results indicate that precise insights into development and mutagenesis of normal human cells will be possible."
This experiment used healthy mice. If mutation rates are similar in human cells, these techniques could be used to provide an insight into the life histories of normal human cells.
"Much more extensive application of this approach will allow us to provide a clear picture of how adult cells have developed from the fertilized egg. Furthermore, by looking at the numbers and types of mutation in each cell we will be able to obtain a diary, writ in DNA, of what each healthy cell has experienced during its lifetime, and then explore how this changes in the range of human diseases," pointed out Mike Stratton, Ph.D., director of the Sanger Institute.